The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1,024 OCD patients and 1,028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC=0.702) than unmedicated (AUC=0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level

Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

Objectives: To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA). Methods: Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high). Results: In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (<0.1 μg/ml) at 3 and 6 mg/kg but were greater than 2 μg/ml at 10 mg/kg, whereas the levels were approximately 1 μg/ml for each dosage group in TNF-low patients. Conclusion: In patients with RA, baseline-TNF is significantly associated with the clinical response to infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab

A common brain network among state, trait, and pathological anxiety from whole-brain functional connectivity

Anxiety is one of the most common mental states of humans. Although it drives us to avoid frightening situations and to achieve our goals, it may also impose significant suffering and burden if it becomes extreme. Because we experience anxiety in a variety of forms, previous studies investigated neural substrates of anxiety in a variety of ways. These studies revealed that individuals with high state, trait, or pathological anxiety showed altered neural substrates. However, no studies have directly investigated whether the different dimensions of anxiety share a common neural substrate, despite its theoretical and practical importance. Here, we investigated a brain network of anxiety shared by different dimensions of anxiety in a unified analytical framework using functional magnetic resonance imaging (fMRI). We analyzed different datasets in a single scale, which was defined by an anxiety-related brain network derived from whole brain. We first conducted the anxiety provocation task with healthy participants who tended to feel anxiety related to obsessive-compulsive disorder (OCD) in their daily life. We found a common state anxiety brain network across participants (1585 trials obtained from 10 participants). Then, using the resting-state fMRI in combination with the participants' behavioral trait anxiety scale scores (879 participants from the Human Connectome Project), we demonstrated that trait anxiety shared the same brain network as state anxiety. Furthermore, the brain network between common to state and trait anxiety could detect patients with OCD, which is characterized by pathological anxiety-driven behaviors (174 participants from multi-site datasets). Our findings provide direct evidence that different dimensions of anxiety have a substantial biological inter-relationship. Our results also provide a biologically defined dimension of anxiety, which may promote further investigation of various human characteristics, including psychiatric disorders, from the perspective of anxiety

Swift and Suzaku Observations of the X-Ray Afterglow from the GRB 060105

Results are presented of early X-ray afterglow observations of GRB 060105 by Swift and Suzaku. The bright, long gamma-ray burst GRB 060105 triggered the Swift Burst Alert Telescope (BAT) at 06:49:28 on 5 January 2006. The Suzaku team commenced a pre-planned target of opportunity observation at 19 ks (5.3 hr) after the Swift trigger. Following the prompt emission and successive very steep decay, a shallow decay was observed from T_0+187 s to T_0+1287 s. After an observation gap during T_0 +(1.5-3) ks, an extremely early steep decay was observed in T_0+(4-30) ks. The lightcurve flattened again at T_0+30 ks, and another steep decay followed from T_0+50 ks to the end of observations. Both steep decays exhibited decay indices of 2.3 - 2.4. This very early break, if it is a jet break, is the earliest case among X-ray afterglow observations, suggesting a very narrow jet whose opening angle is well below 1 degree. The unique Suzaku/XIS data allow us to set very tight upper limits on line emission or absorption in this GRB. For the reported pseudo-redshift of z=4.0+/-1.3 the upper limit on the iron line equivalent width is 50 eV.Comment: 8 pages, 5 figures, Accepted for publication in PASJ Suzaku Special Issue (vol. 58

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Investigation of the Chemical Characteristics of Individual Radioactive Microparticles Emitted from Reactor 1 by the Fukushima Daiichi Nuclear Power Plant Accident by Using Multiple Synchrotron Radiation X-ray Analyses

Seven radioactive particles were separated from a soil sample collected at the Northwest region of the Fukushima Daiichi Nuclear Power Plant (FDNPP). It has been pointed out that the soil is contaminated by radioactive materials emitted from reactor 1 of the FDNPP by the accident that occurred in March, 2011. The physical characteristics of these radioactive particles with –100 μm in diameter and non-uniform shape are clearly different from those of spherical microparticles, known as Cesium-balls, thought to be emitted from the FDNPP reactor 2. Three kinds of synchrotron radiation-based X-ray analyses (X-ray fluorescence analysis, X-ray absorption near edge structure analysis and X-ray diffraction analysis) were nondestructively applied to radioactive particles using a micro-focused X-ray beam at the SPring-8 to investigate their detailed chemical properties. Various elements related to fission products of nuclear fuel and components of the reactor were detected from the particles emitted from the FDNPP reactor 1 with an obvious heterogeneous elemental distribution. In particular, the chemical compositional feature of these particles was characterized by several elements (Sr, Ba etc.), which were easily volatilized in a reducing atmosphere. Although a main component of the particles was identified as silicate glass similar to the Cesium-balls, some crystalline materials were also found in microscopic regions containing Fe and other metallic elements. We concluded that these radioactive particles were emitted from reactor 1 to the atmosphere during 12th to 13th March, 2011. Our results suggest the fact that the nuclear fuel and the reactor vessels around the fuel were melted together at a very early stage of the accident. In addition, it was demonstrated that chemical compositional information of individual radioactive materials can be a new indicator as an alternative to the radioactive ratio to estimate the source of emissions

Ryugu’s nucleosynthetic heritage from the outskirts of the Solar System

Little is known about the origin of the spectral diversity of asteroids and what it says about conditions in the protoplanetary disk. Here, we show that samples returned from Cb-type asteroid Ryugu have Fe isotopic anomalies indistinguishable from Ivuna-type (CI) chondrites, which are distinct from all other carbonaceous chondrites. Iron isotopes, therefore, demonstrate that Ryugu and CI chondrites formed in a reservoir that was different from the source regions of other carbonaceous asteroids. Growth and migration of the giant planets destabilized nearby planetesimals and ejected some inward to be implanted into the Main Belt. In this framework, most carbonaceous chondrites may have originated from regions around the birthplaces of Jupiter and Saturn, while the distinct isotopic composition of CI chondrites and Ryugu may reflect their formation further away in the disk, owing their presence in the inner Solar System to excitation by Uranus and Neptune